title: Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis.
abstract: OBJECTIVE
  Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis.
  
  
  METHODS
  We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173).
  
  
  RESULTS
  Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013).
  
  
  CONCLUSIONS
  In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.
authors.affiliation: Department of Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia; Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: sanaifa@ngha.med.sa.
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Sanai
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Babatin
authors.forename: Khalid I
authors.initials: KI
authors.lastname: Bzeizi
authors.forename: Fahad
authors.initials: F
authors.lastname: Alsohaibani
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Hamoudi
authors.forename: Khaled O
authors.initials: KO
authors.lastname: Alsaad
authors.forename: Hadeel
authors.initials: H
authors.lastname: Al Mana
authors.forename: Fayaz A
authors.initials: FA
authors.lastname: Handoo
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Ashgar
authors.forename: Hamdan
authors.initials: H
authors.lastname: Alghamdi
authors.forename: Abeer
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Aljumah
authors.forename: Abduljaleel
authors.initials: A
authors.lastname: Alalwan
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Altraif
authors.forename: Hussa
authors.initials: H
authors.lastname: Al-Hussaini
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
authors.forename: Ayman A
authors.initials: AA
authors.lastname: Abdo
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006302:Health Services Research; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase
keywords: AASLD; AFP; ALT; APASL; AST; AUROC; Alanine Aminotransferase; American Association for the Study of Liver Diseases; Asian-Pacific Association for the Study of the Liver; CI; Diagnosis; EASL; European Association for the Study of the Liver; Fibrosis; HBV; HBV DNA; HBeAg; HBsAg; Hepatitis B; LR; Liver Disease; Management; NPV; PPV; Sensitivity; Specificity; ULN; USPA; United States Panel Algorithm; alanine aminotransferase; area under the receiver operating characteristic; aspartate aminotransferase; confidence interval; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; likelihood ratio; negative predictive value; positive predictive value; upper limit of normal; α-fetoprotein